TsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>

ABSTRACT Pathogenic strains of Vibrio cholerae require careful regulation of horizontally acquired virulence factors that are largely located on horizontally acquired genomic islands (HAIs). While TsrA, a Vibrionaceae-specific protein, is known to regulate the critical HAI virulence genes toxT and c...

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Autores principales:	Cory D. DuPai, Ashley L. Cunningham, Aaron R. Conrado, Claus O. Wilke, Bryan W. Davies
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Vibrio cholerae gene regulation H-NS TsrA computational biology genetics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/241265e24b73482fa8bf8512cae96ce7
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spelling	oai:doaj.org-article:241265e24b73482fa8bf8512cae96ce72021-11-15T15:31:13ZTsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>10.1128/mSphere.01014-202379-5042https://doaj.org/article/241265e24b73482fa8bf8512cae96ce72020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.01014-20https://doaj.org/toc/2379-5042ABSTRACT Pathogenic strains of Vibrio cholerae require careful regulation of horizontally acquired virulence factors that are largely located on horizontally acquired genomic islands (HAIs). While TsrA, a Vibrionaceae-specific protein, is known to regulate the critical HAI virulence genes toxT and ctxA, its broader function throughout the genome is unknown. Here, we find that deletion of tsrA results in genomewide expression patterns that heavily correlate with those seen upon deletion of hns, a widely conserved bacterial protein that regulates V. cholerae virulence. This correlation is particularly strong for loci on HAIs, where all differentially expressed loci in the ΔtsrA mutant are also differentially expressed in the Δhns mutant. Correlation between TsrA and H-NS function extends to in vivo virulence phenotypes where deletion of tsrA compensates for the loss of ToxR activity in V. cholerae and promotes wild-type levels of mouse intestinal colonization. All in all, we find that TsrA broadly controls V. cholerae infectivity via repression of key HAI virulence genes and many other targets in the H-NS regulon. IMPORTANCE Cholera is a potentially lethal disease that is endemic in much of the developing world. Vibrio cholerae, the bacterium underlying the disease, infects humans utilizing proteins encoded on horizontally acquired genetic material. Here, we provide evidence that TsrA, a Vibrionaceae-specific protein, plays a critical role in regulating these genetic elements and is essential for V. cholerae virulence in a mouse intestinal model.Cory D. DuPaiAshley L. CunninghamAaron R. ConradoClaus O. WilkeBryan W. DaviesAmerican Society for MicrobiologyarticleVibrio choleraegene regulationH-NSTsrAcomputational biologygeneticsMicrobiologyQR1-502ENmSphere, Vol 5, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Vibrio cholerae gene regulation H-NS TsrA computational biology genetics Microbiology QR1-502
spellingShingle	Vibrio cholerae gene regulation H-NS TsrA computational biology genetics Microbiology QR1-502 Cory D. DuPai Ashley L. Cunningham Aaron R. Conrado Claus O. Wilke Bryan W. Davies TsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>
description	ABSTRACT Pathogenic strains of Vibrio cholerae require careful regulation of horizontally acquired virulence factors that are largely located on horizontally acquired genomic islands (HAIs). While TsrA, a Vibrionaceae-specific protein, is known to regulate the critical HAI virulence genes toxT and ctxA, its broader function throughout the genome is unknown. Here, we find that deletion of tsrA results in genomewide expression patterns that heavily correlate with those seen upon deletion of hns, a widely conserved bacterial protein that regulates V. cholerae virulence. This correlation is particularly strong for loci on HAIs, where all differentially expressed loci in the ΔtsrA mutant are also differentially expressed in the Δhns mutant. Correlation between TsrA and H-NS function extends to in vivo virulence phenotypes where deletion of tsrA compensates for the loss of ToxR activity in V. cholerae and promotes wild-type levels of mouse intestinal colonization. All in all, we find that TsrA broadly controls V. cholerae infectivity via repression of key HAI virulence genes and many other targets in the H-NS regulon. IMPORTANCE Cholera is a potentially lethal disease that is endemic in much of the developing world. Vibrio cholerae, the bacterium underlying the disease, infects humans utilizing proteins encoded on horizontally acquired genetic material. Here, we provide evidence that TsrA, a Vibrionaceae-specific protein, plays a critical role in regulating these genetic elements and is essential for V. cholerae virulence in a mouse intestinal model.
format	article
author	Cory D. DuPai Ashley L. Cunningham Aaron R. Conrado Claus O. Wilke Bryan W. Davies
author_facet	Cory D. DuPai Ashley L. Cunningham Aaron R. Conrado Claus O. Wilke Bryan W. Davies
author_sort	Cory D. DuPai
title	TsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>
title_short	TsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>
title_full	TsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>
title_fullStr	TsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>
title_full_unstemmed	TsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>
title_sort	tsra regulates virulence and intestinal colonization in <italic toggle="yes">vibrio cholerae</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/241265e24b73482fa8bf8512cae96ce7
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TsrA Regulates Virulence and Intestinal Colonization in <italic toggle="yes">Vibrio cholerae</italic>

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